Ketogenic Diet Variations for Type 2 Diabetes and Obesity

(KETO-IM Trial)

Overseen By Paulina Blanco Cervantes, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Disqualifiers: Pregnancy, Dialysis, Familial hypercholesterolemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

175 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Keto-CAN, Ketogenic Diet with Canola Oil, KETO-Can, Keto-SAT, Ketogenic Diet High in Saturated Fat, KETO-Sat, Traditional Ketogenic Diet, LFD, Low-Fat Diet for Type 2 Diabetes and Obesity?

Research suggests that ketogenic diets can be beneficial for weight loss and glucose control in people with diabetes, as seen in older patients where 54% achieved better glucose control and 79% lost weight. Additionally, a low-carbohydrate, ketogenic diet may improve blood sugar levels and reduce the need for diabetes medications. ^{1 2 3 4 5}

Is the ketogenic diet generally safe for humans?

Based on available evidence, a well-formulated ketogenic diet does not appear to have major safety concerns for the general public and can be considered a first-line approach for obesity and diabetes. However, some adverse events like changes in cholesterol levels, constipation, and fatigue have been reported, so it's important to monitor health while on the diet. ^{1 3 5 6 7}

How is the Keto-CAN and Keto-SAT treatment different from other treatments for type 2 diabetes and obesity?

The Keto-CAN and Keto-SAT treatments are unique because they are variations of the ketogenic diet, which is high in fat and low in carbohydrates, designed to induce ketosis (a state where the body burns fat for fuel). Keto-CAN uses canola oil, which is high in polyunsaturated fats, potentially offering better insulin sensitivity and lipid profiles compared to traditional saturated fat-rich ketogenic diets like Keto-SAT. This approach contrasts with low-fat diets, which have been less effective in managing obesity and diabetes. ^{1 2 5 6 8}

What is the purpose of this trial?

The goal of this clinical trial is to compare a healthy KETO diet supplemented with canola oil (KETO-Can) compared to a traditional KETO diet high in saturated fat (KETO-Sat) and low-fat diet (LFD) in adults at high risk of or diagnosed with type 2 diabetes. The main question\[s\] it aims to answer are: * Effects on CVD risk factors (plasma cholesterol, TG, ApoB100, glucose, insulin and HbA1C). * Effects on systemic inflammation and immune function. * Adherence to interventions. Participants will be randomized into 1 of the dietary treatments during which they will follow a Keto or a low-fat diet. Comparisons among groups at 3 and 6 months of intervention will be conducted.

Research Team

Catherine Chan, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for adults with obesity or overweight and HbA1C levels at or above 5.7%, indicating high blood sugar, which can be a sign of prediabetes or diabetes. It's not suitable for individuals with certain cholesterol or triglyceride disorders, those undergoing menopause, on dialysis, transitioning transgender individuals, pregnant women, or anyone whose diet wouldn't allow them to follow the study's nutritional guidelines.

Inclusion Criteria

You are overweight or obese and have high HbA1C levels.

Exclusion Criteria

I have a family history of high cholesterol or high triglycerides.

I am on dialysis or advised to eat a low-protein diet due to kidney function.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into one of three dietary treatments (KETO-Can, KETO-Sat, or LFD) and receive nutrition counseling for 6 months.

6 months

Monthly visits for dietary assessment and counseling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Keto-CAN
• Keto-SAT
• LFD

Trial Overview The study is testing three diets: a ketogenic diet supplemented with saturated fat (Keto-SAT), a ketogenic diet supplemented with canola oil (Keto-CAN), and a low-fat diet (LFD). Participants will be randomly assigned to one of these diets to see how they affect heart disease risk factors like cholesterol and blood sugar levels as well as inflammation and immune function over periods of 3 and 6 months.

Participant Groups

Group I: KETO-Sat Experimental Treatment 1 Intervention

KETO diet supplemented with butter and coconut oil (high in SFA).

Group II: KETO-Can Experimental Treatment 1 Intervention

KETO diet supplemented with Canola oil (high in MUFA and omega-3 FA).

Group III: Low fat diet (LFD) Active Control 1 Intervention

Low fat diet supplemented with whole grain foods (pasta or brown rice) and oatmeal.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Findings from Research

In a study involving 11 healthy, normal-weight participants, a high-fat ketogenic diet (KD) did not improve cognitive function, mood, or sleep quality compared to a high-carbohydrate, low-fat diet over a 3-week period.

Despite achieving nutritional ketosis, the KD showed no significant effects on tasks measuring vigilance, memory, or executive function, indicating that this diet may not enhance cognitive performance in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. Iacovides, S., Goble, D., Paterson, B., et al.[2023]

Long-term consumption of a ketogenic diet in rats led to significant weight loss, decreased blood sugar levels, and increased blood ketones, indicating effective metabolic changes associated with this diet.

However, the ketogenic diet also resulted in metabolic acidosis and anemia, as evidenced by lower blood pH and reduced levels of erythrocytes, hemoglobin, and hematocrit, alongside a decrease in antioxidant enzyme superoxide dismutase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats. Arsyad, A., Idris, I., Rasyid, AA., et al.[2022]

In a study of 200 older patients (median age 70) on a ketogenic diet, 67% reported beneficial outcomes, including significant weight loss for 79% of those seeking it, improved glucose control for 54% of those with diabetes, and positive effects on cancer outcomes for 63% of patients pursuing that goal.

While the ketogenic diet showed promise for various health issues in older adults, 15% of participants experienced adverse events, including dyslipidemia and constipation, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. Almodallal, Y., Cook, K., Lammert, LM., et al.[2023]

In a 16-week study involving 28 overweight participants with type 2 diabetes, the low-carbohydrate, ketogenic diet (LCKD) led to a significant 16% reduction in hemoglobin A1c levels, indicating improved glycemic control.

The diet also allowed for the discontinuation or reduction of diabetes medications in 17 out of 21 participants who completed the study, highlighting the need for close medical supervision when implementing such dietary changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Yancy, WS., Foy, M., Chalecki, AM., et al.[2020]

A polyunsaturated fat-enriched ketogenic diet (POLY KD) led to higher levels of ketosis and improved insulin sensitivity in healthy adults compared to a saturated fat-enriched ketogenic diet (SAT KD) over a 5-day period.

The POLY KD did not negatively impact cholesterol levels, unlike the SAT KD, suggesting that the POLY KD may be a safer and more effective option for long-term use in managing conditions like epilepsy and metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets. Fuehrlein, BS., Rutenberg, MS., Silver, JN., et al.[2022]

Ketogenic diets, which consist of over 70% fat and very low carbohydrates, may be more effective than low-fat diets for treating obesity and diabetes, showing potential benefits in reducing blood glucose and insulin levels.

A well-formulated ketogenic diet appears to be safe for the general public and could be considered a first-line treatment for obesity and diabetes, although more high-quality clinical trials are needed to explore its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. Ludwig, DS.[2023]

A 4-year-old girl with a rare FBXL4 gene mutation and severe lactic acidosis was successfully treated with a ketogenic diet (KD) after standard treatments failed, highlighting the KD's potential in managing mitochondrial disorders.

This case represents the first documented use of parenteral KD to effectively reduce lactic acidosis in a patient with mitochondrial depletion syndrome, suggesting a promising nonpharmacological intervention for similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. İnci, A., Aktaş, E., Cengiz Ergin, FB., et al.[2022]

The ketogenic diet (KD) has shown beneficial effects in managing diabetes, obesity, and other endocrine disorders, including improved glycemic control and significant weight loss, based on a review of its clinical applications.

KD is also associated with positive outcomes in cardiac health and respiratory function, and a vegetarian variant has been developed to accommodate specific dietary preferences, highlighting its versatility as a therapeutic diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet in endocrine disorders: Current perspectives. Gupta, L., Khandelwal, D., Kalra, S., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. [2023]

4. England pubmed.ncbi.nlm.nih.gov

A low-carbohydrate, ketogenic diet to treat type 2 diabetes. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Ketogenic diet in endocrine disorders: Current perspectives. [2019]